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Biomedical subjects

J E Edwards

Publications and source records attributed to J E Edwards.

At least 181 records · Page 10Linked to original sources

Neutrophil-mediated protection of cultured human vascular endothelial cells from damage by growing Candida albicans hyphae.

Interactions were studied between human neutrophils and cultured human umbilical vein endothelial cells invaded by Candida albicans. In the absence of neutrophils, progressive Candida germination and hyphal growth extensively damaged endothelial cell monolayers over a period of 4 to 6 hours, as determined both by morphological changes and release of 51Cr from radiolabeled endothelial cells. Monolayers were completely destroyed and replaced by hyphae after 18 hours of incubation. In contrast, when added 2 hours after the monolayers had been infected with Candida, neutrophils selectively migrated toward and attached to hyphae at points of hyphal penetration into individual endothelial cells (observed by time-lapse video-microscopy). Attached neutrophils spread over hyphal surfaces both within and beneath the endothelial cells; neutrophil recruitment to initial sites of leukocyte-Candida-endothelial cell interactions continued throughout the first 60 minutes of observation. Neutrophil spreading and stasis were observed only along Candida hyphae and at sites of Candida-endothelial cell interactions. These events resulted in 58.0% killing of Candida at 2 hours and subsequent clearance of Candida from endothelial cell monolayers, as determined by microcolony counts and morphological observation. On introduction of additional neutrophils to yield higher ratios of neutrophils to endothelial cells (10 neutrophils:1 endothelial cell), neutrophil migration toward hyphal elements continued. Despite retraction or displacement of occasional endothelial cells by invading Candida and neutrophils, most endothelial cells remained intact, viable, and motile as verified both by morphological observations and measurement of 51Cr release from radiolabeled monolayers. From these studies, we conclude that neutrophils are capable of killing Candida hyphae selectively within human vascular endothelial cell monolayers and may have protective rather than detrimental effects on endothelial cell integrity.

Candida albicans↗

Vascular ring in interruption of the aortic arch with bilateral patent ductus arteriosi.

The previously unreported occurrence of a true vascular ring in association with interruption of the aortic arch resulting from bilateral persistence of the ductus arteriosi is described. Division of both ductus is necessary to minimize the potential for tracheobronchial compression. This should be accomplished either during definitive (one-stage) repair of the interrupted aortic arch and associated anomalies or at the initial procedure of a staged repair.

Aorta, Thoracic↗

Expression of specific binding sites on Candida with functional and antigenic characteristics of human complement receptors.

Receptors for C3 degradation fragments (CR1, CR2, and CR3) are present on many human cells including phagocytes and lymphoid cells and may be critical in the attachment of invading microorganisms. In these studies Candida were found to mimic the human CR by binding erythrocytes coated with specific human C3 fragments. Yeast forms of Candida species were adhered to glass slides and were allowed to germinate. Sheep erythrocytes (E) were coated with IgM (EA) and human complement components to prepare EA, EAC14, EAC3b, EAC3bi, and EAC3d. These test cells were then examined for adherence to the organism. Antibodies to human CR1, CR2, and CR3 were used to evaluate their potential for blocking adherence of the test erythrocytes to Candida. Fluorescein-labeled antibodies to human complement receptors were also used to characterize the binding sites. EAC3bi and EAC3d, but not E, EA, or EAC14, bound extensively to the germ tubes and pseudohyphae of Candida albicans and C. stellatoidea. EAC3b bound infrequently. Other Candida species, generally considered less pathogenic, bound significantly fewer specific test erythrocytes than C. albicans. Monoclonal antibodies to human CR1 and CR3 (3D9, 1B4, C511, 2B6, anti-B2, Mo1, and anti-Mac-1), in general, did not block adherence of test erythrocytes. Blocking of adherence of EAC3bi and EAC3d test erythrocytes coated with small quantities of C3 fragments occurred with high concentrations of monoclonal (anti-CR2) HB-5 and polyclonal (anti-CR2) anti-GP 140. Immunofluorescence studies demonstrated binding of Mo-1 to the germinated forms of the organism, whereas binding of the other antibodies was not seen. These studies suggest a surface constituent on the organism similar to CR on human cells. Additional studies are necessary to further define the molecular nature of the binding site. The ability of organisms to mimic human CR may be more generalized than previously known and may serve as a mechanism for modification of the inflammatory and immune response.

Antibodies, Monoclonal↗

New guidelines for the clinical diagnosis of mitral valve prolapse.

Because the term mitral valve prolapse has pathologic connotations, considerable effort has been expended to establish acceptable diagnostic standards, but without general agreement. This report combines information from the history, physical examination, electrocardiogram, chest x-ray and 2-dimensional echocardiogram in an effort to avoid the artifice of using the 2-dimensional echocardiogram as a categoric reference standard and to establish new clinical guidelines that distinguish pathologic mitral valve prolapse--a primary connective tissue abnormality of leaflets, chordae tendineae and anulus--from normal superior systolic displacement of mitral leaflets. The objective is to avoid implications of heart disease in healthy young persons within the gaussian distribution of normal. To this end, and with the Jones criteria as a model, major and minor criteria are proposed for the clinical diagnosis of mitral valve prolapse as a pathologic entity.

Angiocardiography↗

Congenital unilateral pulmonary venous atresia with pulmonary veno-occlusive disease in contralateral lung: an unusual association.

A patient presenting with the rare association of congenital unilateral pulmonary venous atresia in one lung and pulmonary veno-occlusive disease in the other is described. The patient first presented at the age of 3 1/2 years with anemia, hemoptysis, and pulmonary hypertension. After cardiac catheterization and angiocardiography, a diagnosis of atresia of the left pulmonary veins was made for which left pneumonectomy was done. Four years later the patient presented with right-sided congestive failure and radiologic evidence of right-sided pulmonary edema from which death resulted. At autopsy, the right lung showed changes of pulmonary veno-occlusive disease, while the major veins were not involved.

Child↗

Scimitar syndrome in neonates: report of four cases and review of the literature.

Four neonates with scimitar syndrome are presented. Three of the cases had congenital cardiovascular abnormalities not usually regarded as part of the scimitar syndrome, namely, ventricular septal defect, abnormalities of the aortic arch, and abnormal relationship of the pulmonary arteries and bronchi. Review of the literature indicates that among subjects of all ages the incidence of additional congenital heart disease is 24%; in patients within the pediatric age group the incidence is about 36% and is highest (75%) among those subjects having diagnostic studies while neonates.

Bronchi↗

Persistent truncus arteriosus: pathologic anatomy in 54 cases.

Fifty-four specimens of heart with persistent truncus arteriosus (PTA) were reviewed anatomically. According to the Collett-Edwards classification there were 28 examples of type I and 26 type II. The sex distribution was equal. The number of the truncal cusps ranged from one to four (42% tricuspid, 30% bicuspid, 24% quadricuspid, and 4% unicommissural). A unicommissural truncal valve has not been previously reported. In 72% of cases, the truncal valve leaflets were thickened or dysplastic. Two valves were stenotic. The truncus arteriosus originated from both ventricles equally in 42% of the cases, predominantly from the right ventricle in 42%, and predominantly from the left ventricle in 16% of the cases. In unoperated cases of PTA originating predominantly from the right ventricle, it appeared to us that usual operative correction might result in left ventricular outflow obstruction. Variations in coronary arterial origins and patterns were present in nearly half of the cases. A single coronary artery was observed in ten cases (18.5%). Stenosis of the ostium of one coronary artery was seen in each of four cases (7%). High posterior origin of the left coronary artery was observed in ten cases (18.5%). Among the associated cardiovascular anomalies, the most common were right aortic arch (36%) and interruption of the aortic arch (11%). Three cases with the latter condition exhibited crossed pulmonary arteries. Isolated cases with tricuspid atresia, vascular sling (left pulmonary artery arising from right pulmonary artery), and persistent common atrioventricular canal were encountered.

Adolescent↗

Ventricular inversion with normally connected great vessels in situs solitus (atrioventricular discordance with ventriculoarterial concordance).

A patient with ventricular inversion, normally connected great vessels, and aortic valvular atresia is presented. The case represents an association of two rare situations. The first of these is normally connected great vessels with ventricular inversion. The second is the association of commonly occurring aortic valvular atresia with ventricular inversion.

Aortic Valve↗

Single papillary muscle of the left ventricle associated with persistent common atrioventricular canal: variant of parachute mitral valve.

Six cases of single papillary muscle of the left ventricle in persistent common atrioventricular canal (AVC) are described. Except for one case with double outlet right ventricle and AVC, in the other five cases AVC occurred with normally related great vessels. Down's syndrome was present in two cases. The mitral valvular condition in AVC is not the classic parachute mitral valve since the separation between the common anterior and the common posterior leaflet leaves a space (cleft) oriented toward the ventricular septum. This mitral valve in AVC may or may not be obstructive. The common anterior leaflet fixed to the ventricular septum may result in obstruction. Clinically, single left ventricular papillary muscle should be suspected if the AVC is associated with coarctation of the aorta or tubular hypoplasia of the aortic arch. This type of mitral valve in AVC may also be associated with double outlet right ventricle. Preoperative recognition of the single papillary muscle by echocardiogram or left ventriculogram will prevent postoperative mitral obstruction following closure of the mitral cleft.

Aortic Coarctation↗

Predictive value of lung biopsy in ventricular septal defect: long-term follow-up.

Although the Heath-Edwards classification has been used for more than 25 years to evaluate pulmonary vascular changes, its potential to predict the long-term course after successful ventricular septal defect closure has not been proved. Operative lung biopsy slides obtained at the time of closure from 57 infants and children who had been among the first survivors (between 1954 and 1960) of such surgery were graded in blinded fashion according to the Heath-Edwards classification system, and the resultant biopsy grade of each was compared with the eventual long-term outcome of each child. In 53 (93%) of the 57 cases, the Heath-Edwards system correlated well with long-term clinical or hemodynamic status of the patient. Grade IV changes were predictive of a usually fatal outcome, while grade I and II changes were generally benign. Death from pulmonary vascular disease occurred, however, in four children whose operative lung biopsy had been classified as either grade I or II, indicating that the focal nature of the higher Heath-Edwards grades, or human error, must be considered when this classification system is employed.

Adolescent↗

Ectopic origin of a coronary artery from the aorta. Sudden death in 3 of 23 patients.

Ectopic origin of a coronary artery from the aorta is uncommon. In the last decade, its importance as a possible cause of sudden death has been documented. Initially, only the left coronary artery was implicated. Lately, the ectopically arising right coronary artery has also been shown to be involved in cases of sudden death. We reviewed the pathologic anatomy in 23 cases of ectopic origin of a coronary artery from the aorta. In three of these cases, death could be attributed to ectopic origin of a coronary artery. In one case the left coronary artery arose from the right aortic sinus, and in two cases the right coronary artery arose from the left aortic sinus. In one of these, a scar of healed myocardial infarction was present in the inferior wall of the left ventricle. The possible mechanism for sudden death in these cases is reviewed and emphasis placed on the theory that the acute angle at which the ectopic artery leaves the aorta results in a flap-like mechanism at the arterial ostium. Ostial stenosis by the flap could be a significant factor in causing myocardial ischemia in some patients and also in sudden death.

Adolescent↗

Mycotic aneurysms of the aortic root. A pathologic study of 20 cases.

Twenty specimens of heart with mycotic aneurysms at the aortic root were studied. In ten cases, mycotic aneurysm followed infection of the aortic valve. In one case, it developed following infection of an aortic jet lesion, and in nine patients, the aneurysm was at the seat of a prosthetic aortic valve. In seven of the 11 cases with a natural aortic valve, the valve was either unicuspid or bicuspid. A retrospective evaluation of the data on the clinical records of the 20 patients revealed that infective endocarditis or noncardiac postoperative sepsis was present in 11. The most frequently isolated microorganism was Staphylococcus aureus. Conduction disturbances were found in six patients, all of them with involvement of the atrioventricular node by the aneurysm. Perforation into intracardiac cavities was found in four, two into the right ventricular infundibulum and one each into each atrium. Pericardial tamponade was caused by bleeding from the aneurysm in two cases, and myocardial infarction was a probable consequence of coronary arterial compression by the aneurysm in two cases. Mycotic aneurysms of the aortic root, in spite of their being partially or completely healed of active infection, carry a high risk of the complications enumerated. Among the 20 cases, cultures were positive in 11 and negative in nine. Staphylococcus aureus was cultured from five of the cases.

Adult↗

Accessory tissue of the tricuspid valve protruding into the left ventricle through a septal defect.

We report the pathologic findings in 13 cases with accessory tissue originating from the tricuspid valve and protruding into the left ventricular outflow tract through a ventricular septal defect (VSD). In eight cases the accessory tissue formed a pouch, the walls of which were similar to the tissue of the normal tricuspid valve. In five cases, papillarylike masses of young connective tissue formed the accessory tissue. The degree of left ventricular outflow tract obstruction was mild in five cases, intermediate in five, and severe in three. Adhesions to the rims of the VSD causing obstruction of the VSD were seen in ten cases. Associated anomalies were present in all cases. The most frequent associated anomalies other than the tricuspid valvular anomalies and the VSDs were transposition of the great arteries and a variety of vascular anomalies.

Child, Preschool↗

Mitral valve prolapse and ruptured chordae tendineae.

To determine the causes of ruptured chordae tendineae and a suspected etiologic role for mitral valve prolapse (MVP), the mitral valve in 25 consecutive and surgically proved cases of chordal rupture were examined. The diagnosis of MVP was made on the basis of redundancy and marked hooding of the mitral leaflets and on histologic changes. MVP was the underlying morphologic abnormality in 23 patients, only 1 of whom had infective endocarditis that was responsible for the rupture. Thus MVP was the only underlying morphologic abnormality in 22 of 25 patients (88%). Another finding in this study was the demonstration of auscultatory and angiographic or echocardiographic evidence of MVP in 4 patients, aged 4 to 11 years (mean 7), before chordal rupture; no patient had had endocarditis. The morphologic and historical evidence would indicate that MVP is probably the most common cause of so-called spontaneous chordal rupture.

Adult↗

Aneurysm of the fossa ovalis in infants: a pathologic study.

An aneurysm of the fossa ovalis was identified at autopsy in 17 infants. In each case the aneurysm of the fossa ovalis was considered to have resulted from excessive elevation of pressure in that atrium contralateral to the side into which the aneurysm bulged. The aneurysms were divided into two types: intrinsic (three cases) and extrinsic (14 cases). The intrinsic types of aneurysms of the fossa ovalis were considered to have started in fetal life and were consequences of abnormally narrow states of interatrial ostium II. Each intrinsic aneurysm bulged toward the left. Among the extrinsic types of aneurysm of the fossa ovalis, each was considered to have resulted from the hemodynamic consequences of a congenital anomaly in one side of the heart or other. Six aneurysms of extrinsic type bulged toward the left and eight toward the right. Aneurysm of the fossa ovalis should be included in the differential diagnosis of space-occupying conditions within the atria.

Female↗

The disease-free wall in coronary atherosclerosis: its relation to degree of obstruction.

Coronary atherosclerotic lesions are more often located eccentrically (70%) than concentrically (30%). In this study, the configuration of eccentric coronary artery atherosclerotic lesions was assessed by means of computerized planimetry in 100 specimens of eccentric arterial lesions. Special attention was given to the relation between the disease-free wall and the severity of obstruction. The mean disease-free wall are length measured between 17 and 23% of the total vessel circumference in eccentric coronary artery lesions that obstructed 50 to 90% of the cross-sectional area. This ratio persisted irrespective of the location of the lesion within the vessel and was not significantly different with vessels of different sizes. The presence of disease-free arcs of coronary artery wall as observed in this pathologic study may relate to three factors in clinical coronary artery disease: The published observations of spasm in segments of arteries harboring structural obstructive lesions may be explained by the frequent presence of uninvolved arcs of coronary artery walls. Multiple views during coronary arteriography are necessary to accurately reflect the degree of obstruction. The results of percutaneous transluminal coronary angioplasty may be influenced by both the disease-free arc and the atheromatous obstruction.

Angioplasty, Balloon↗

Adherence of Candida to cultured vascular endothelial cells: mechanisms of attachment and endothelial cell penetration.

To elucidate the pathogenesis of hematogenous Candida infections, we developed an in vitro model of Candida adherence to and penetration of human endothelial cells. We enhanced or inhibited adherence in order to probe mechanisms of attachment. Adherence of Candida albicans showed a linear relation to Candida inoculum (range, 10(2)-10(5) cfu, r = .99, P less than .01) and exceeded that of less virulent Candida species and that of Saccharomyces cerevisiae (P less than .01). Candida immune serum blocked attachment (greater than 95% inhibition; P less than .001), however, this activity was abolished by immunoprecipitation of immune serum with C. albicans mannan (P less than .001) and was unaffected by immunoprecipitation with S. cerevisiae mannan or by adsorption with particulate chitin. Adherence was diminished by exposing C. albicans to heat (greater than 99% inhibition; P less than .01), UV light (98% inhibition; P less than .01), or sodium periodate (greater than 72% inhibition; P less than .01). An extract from heat-exposed C. albicans blocked adherence (greater than 51% inhibition; P less than .001). Transmission electron microscopy demonstrated that viable or killed Candida organisms were attached to endothelial cells, were enveloped by membrane processes from the endothelial cell surface, and were incorporated into the endothelial cells within phagosomes. Cytochalasin B blocked incorporation without blocking surface attachment.

Adhesiveness↗